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This study was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.
This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afegostat tartrate 25 milligrams (mg) once per day | Experimental | Afegostat tartrate was administered orally during the 4-week treatment period. |
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| Afegostat tartrate 150 mg once per day | Experimental | Afegostat tartrate was administered orally once per day during the 4-week treatment period. |
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| Afegostat tartrate 150 mg once every four days | Experimental | Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period. |
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| Afegostat tartrate 150 mg once every seven days | Experimental | Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afegostat tartrate | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Day 1 (after dosing) through Day 35 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC) | GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug. | Baseline, Day 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor, Clinical Research | Amicus Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco | California | 94143 | United States | |||
Participants were screened for evaluation of eligibility to participate in the study. Confirmatory β-glucosidase genotype testing was done at screening to confirm reported genotype. Thirty participants received at least 1 dose of study drug. All participants were eligible for inclusion in the safety and 29 in the pharmacodynamics (PD) populations.
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| ID | Title | Description |
|---|---|---|
| FG000 | Afegostat Tartrate 25 Milligrams (mg) Once Per Day | Afegostat tartrate was administered orally during the 4-week treatment period. |
| FG001 | Afegostat Tartrate 150 mg Once Per Day |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Coral Springs |
| Florida |
| 33065 |
| United States |
| Decatur | Georgia | 30033 | United States |
| Iowa City | Iowa | 52242 | United States |
| New York | New York | 10016 | United States |
| Cincinnati | Ohio | 45229 | United States |
| Portland | Oregon | 97239 | United States |
| Philadelphia | Pennsylvania | 19104 | United States |
| Pittsburgh | Pennsylvania | 15213 | United States |
| Houston | Texas | 77030 | United States |
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
| FG002 | Afegostat Tartrate 150 mg Once Every Four Days | Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period. |
| FG003 | Afegostat Tartrate 150 mg Once Every Seven Days | Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period. |
| Safety Population | All participants who received at least 1 dose of study drug. |
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| PD Population | Participants in the Safety Population with a baseline and at least 1 post-baseline PD measurement. |
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| Received at Least One Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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All participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Afegostat Tartrate 25 mg Once Per Day | Afegostat tartrate was administered orally during the 4-week treatment period. |
| BG001 | Afegostat Tartrate 150 mg Once Per Day | Afegostat tartrate was administered orally once per day during the 4-week treatment period. |
| BG002 | Afegostat Tartrate 150 mg Once Every Four Days | Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period. |
| BG003 | Afegostat Tartrate 150 mg Once Every Seven Days | Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Safety Population: all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Day 1 (after dosing) through Day 35 |
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| Secondary | Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC) | GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug. | PD Population: All participants who were included in the Safety Population and had a baseline and at least 1 post-baseline PD measurement. | Posted | Mean | Standard Deviation | pmol/mg/min | Baseline, Day 28 |
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Day 1 (after dosing) to Day 35
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afegostat Tartrate 25 mg Once Per Day | Afegostat tartrate was administered orally during the 4-week treatment period. | 0 | 7 | 4 | 7 | ||
| EG001 | Afegostat Tartrate 150 mg Once Per Day | Afegostat tartrate was administered orally once per day during the 4-week treatment period. | 0 | 7 | 2 | 7 | ||
| EG002 | Afegostat Tartrate 150 mg Once Every Four Days | Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period. | 0 | 9 | 4 | 9 | ||
| EG003 | Afegostat Tartrate 150 mg Once Every Seven Days | Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period. | 0 | 7 | 1 | 7 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | MedDRA (10.1) | Systematic Assessment |
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| Lacrimation increased | Eye disorders | MedDRA (10.1) | Systematic Assessment |
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| Ocular hyperaemia | Eye disorders | MedDRA (10.1) | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Gingival pain | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (10.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (10.1) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (10.1) | Systematic Assessment |
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| Platelets counts decreased | Investigations | MedDRA (10.1) | Systematic Assessment |
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| Red blood cell count decreased | Investigations | MedDRA (10.1) | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
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| Eyelids pruritus | Eye disorders | MedDRA (10.1) | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
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| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
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| Pain | General disorders | MedDRA (10.1) | Systematic Assessment |
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| Fasciitis | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
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| Sinus headache from seasonal allergies | General disorders | MedDRA (10.1) | Systematic Assessment |
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The investigator can publish only the results from this trial, provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review prior to submission for publication. If requested and prior to publication, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Patient Advocacy | +1-609-662-2000 | Clinicaltrials@Alexion.com |
| ID | Term |
|---|---|
| D005776 | Gaucher Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
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| ID | Term |
|---|---|
| C000599126 | AT2101 |
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| Male |
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Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period. |
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